Neutrophil­to­lymphocyte ratio reflects lung injury in thoracic radiotherapy and immune checkpoint inhibitors combination therapy with different sequences.

The combination of thoracic radiotherapy and immune checkpoint inhibitors (ICIs) has emerged as a novel treatment approach for malignant tumors. However, it is important to consider the potential exacerbation of lung injury associated with this treatment modality. The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, holds promise as a non-invasive indicator for assessing the toxicity of this combination therapy. To investigate this further, a study involving 80 patients who underwent thoracic radiotherapy in conjunction with ICIs was conducted. These patients were divided into two groups: The concurrent therapy group and the sequential therapy group. A logistic regression analysis was conducted to ascertain risk factors for grade ≥2 pneumonitis. Following propensity score matching, the NLR values were examined between the concurrent group and the sequential group to evaluate any disparity. A mouse model of radiation pneumonitis was established, and ICIs were administered at varying time points. The morphological evaluation of lung injury was conducted using H&E staining, while the NLR values of peripheral blood were detected through flow cytometry. Logistic regression analysis revealed that radiation dosimetric parameters (mean lung dose, total dose and V20), the inflammatory index NLR at the onset of pneumonitis, and treatment sequences (concurrent or sequential) were identified as independent predictors of grade ≥2 treatment-related pneumonitis. The results of the morphological evaluation indicated that the severity of lung tissue injury was greater in cases where programmed cell death protein 1 (PD-1) blockade was administered during thoracic radiotherapy, compared with cases where PD-1 blockade was administered 14 days after radiotherapy. Moreover, the present study demonstrated that the non-invasive indicator known as the NLR has the potential to accurately reflect the aforementioned injury.

Prognostic value of neuron-specific enolase in patients with advanced and metastatic non-neuroendocrine non-small cell lung cancer.

BACKGROUND: Increased serum neuron-specific enolase (NSE) level was found in a substantial proportion (30-69%) of patients with non-small-cell lung cancer (NSCLC), but little was known about the clinical properties of NSE in NSCLC. OBJECTIVE: We aimed to assess the level of serum NSE to predict prognosis and treatment response in patients with advanced or metastatic non-neuroendocrine NSCLC. METHODS: We retrospectively analyzed 363 patients with advanced and metastatic NSCLC between January 2011 and October 2016. The serum NSE level was measured before initiation of treatment. RESULTS: Patients with high NSE level (≥26.1 ng/ml) showed significantly shorter progression-free survival (PFS) (5.69 vs 8.09 months; P=0.02) and significantly shorter overall survival (OS) than patients with low NSE level (11.41 vs 24.31 months; P=0.01). NSE level was an independent prognostic factor for short PFS (univariate analysis, hazard ratio [HR] = 2.40 (1.71-3.38), P<0.001; multivariate analysis, [HR] = 1.81 (1.28-2.56), P=0.001) and OS (univariate analysis, [HR] = 2.40 (1.71-3.37), P<0.001; multivariate analysis, [HR] = 1.76 (1.24-2.50), P=0.002). CONCLUSION: The survival of NSCLC patients with high serum NSE level was shorter than that of NSCLC patients with low serum NSE levels. Serum NSE level was a predictor of treatment response and an independent prognostic factor.

Assessment of safety margin after microwave ablation of stage I NSCLC with three-dimensional reconstruction technique using CT imaging.

OBJECTIVE: To assess the ablative margin of microwave ablation (MWA) for stage I non-small cell lung cancer (NSCLC) using a three-dimensional (3D) reconstruction technique. MATERIALS AND METHODS: We retrospectively analyzed 36 patients with stage I NSCLC lesions undergoing MWA and analyzed the relationship between minimal ablative margin and the local tumor progression (LTP) interval, the distant metastasis interval and disease-free survival (DFS). The minimal ablative margin was measured using the fusion of 3D computed tomography reconstruction technique. RESULTS: Univariate and multivariate analyses indicated that tumor size (hazard ratio [HR] = 1.91, P < 0.01; HR = 2.41, P = 0.01) and minimal ablative margin (HR = 0.13, P < 0.01; HR = 0.11, P < 0.01) were independent prognostic factors for the LTP interval. Tumor size (HR = 1.96, P < 0.01; HR = 2.35, P < 0.01) and minimal ablative margin (HR = 0.17, P < 0.01; HR = 0.13, P < 0.01) were independent prognostic factors for DFS by univariate and multivariate analyses. In the group with a minimal ablative margin < 5 mm, the 1-year and 2-year local progression-free rates were 35.7% and 15.9%, respectively. The 1-year and 2-year distant metastasis-free rates were 75.6% and 75.6%, respectively; the 1-year and 2-year disease-free survival rates were 16.7% and 11.1%, respectively. In the group with a minimal ablative margin ≥ 5 mm, the 1-year and 2-year local progression-free rates were 88.9% and 69.4%, respectively. The 1-year and 2-year distant metastasis-free rates were 94.4% and 86.6%, respectively; the 1-year and 2-year disease-free survival rates were 88.9% and 63.7%, respectively. The feasibility of 3D quantitative analysis of the ablative margins after MWA for NSCLC has been validated. CONCLUSIONS: The minimal ablative margin is an independent factor of NSCLC relapse after MWA, and the fusion of 3D reconstruction technique can feasibly assess the minimal ablative margin.

Effect and mechanism of peroxisome proliferator-activated receptor-γ on the drug resistance of the U-87 MG/CDDP human malignant glioma cell line.

Peroxisome proliferator-activated receptor-γ (PPAR-γ) is important in tumor differentiation, proliferation and apoptosis. However, the effect and mechanism of PPAR-γ on the promotion of cisplatin sensitivity in glioma cells remain to be elucidated. The present study established cisplatin-resistant U-87 MG/CDDP cell lines and U-87 MG/CDDP cell lines overexpressing PPAR-γ. With upregulated expression of PPAR-γ, the sensitivity of cancer cells to cisplatin was increased. Flow cytometry revealed that the intracellular content of rhodamine-123 was increased, expression of P-glycoprotein was downregulated, cell cycle was arrested in G0/G1 phase, apoptosis and oxidative stress was increased, levels of intracellular thymidylate synthase, glutathione and transforming growth factor-ß1 were decreased, expression levels of multidrug resistance related gene (MDR), multidrug resistance-associated protein and glutothionine S-transferase-π were downregulated, expression levels of cell proliferation and apoptosis associated genes, including survivin and B-cell lymphoma-2, were downregulated, p53, p21 and caspase-3/8 were significantly upregulated, phosphorylation of extracellular signal-regulated kinase and small mothers against decapentaplegic 2 were downregulated, and the transcriptional activities of Twist and nuclear factor (erythroid-derived 2)-like 2 were significantly reduced. The results suggested that upregulation of PPAR-γ in the U-87 MG/DDP cells increased cisplatin sensitivity, and the underlying mechanisms included the regulation of MDR and apoptosis associated genes, which increased the intracellular accumulation of the drug, inhibited cell proliferation and promoted cell apoptosis.

Advantages of CyberKnife for inoperable stage I peripheral non-small-cell lung cancer compared to three-dimensional conformal radiotherapy.

This study was conducted to compare the clinical curative effect and acute radiation lung reactions between CyberKnife (CK) and three-dimensional conformal radiotherapy (3DCRT) treatment for inoperable stage I peripheral non-small-cell lung cancer (NSCLC). We retrospectively analyzed 68 patients with inoperable stage I peripheral NSCLC between 2012 and 2013 in our institution. The CK patients were treated with 42-60 Gy in three fractions, while the 3DCRT patients were treated with a total of 60 Gy, at 2 Gy per fraction. The patients were followed up and the clinical outcome was evaluated according to the Response Evaluation Criteria in Solid Tumours. We assessed the presence of acute radiation pneumonitis and pulmonary function status by thoracic scan and pulmonary function tests following CK and 3DCRT treatment. The binary univariate logistic regression analysis demonstrated that treatment method and forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC) prior to treatment (pre-FEV1/FVC) were the main factors affecting the risk of radiation pneumonitis. The analysis of these factors through multivariate logistic regression method demonstrated that treatment method for grade 1 and 2 [odds ratio (OR)= 7.866 and 11.334, respectively) and pre-FEV1/FVC for grade 1, 2 and 3 (OR = 5.062, 11.498 and 15.042, respectively) were significant factors affecting the risk of radiation pneumonitis (P<0.05). The 68 patients were divided into two subgroups using the threshold of pre-FEV1/FVC selected by the receiver operating characteristic curve. There were significant differences between the 3DCRT and CK treatment in both the pre-FEV1/FVC <68% and ≥68% subgroups for radiation pneumonitis (P=0.023 and 0.002, respectively). There was no statistically significant change in FVC, FEV1 and carbon monoxide diffusion capacity (DCLO) in the CK group, whereas there was a decrease in DCLO in the 3DCRT group. The complete remission rate was 40 vs. 34.2% at 1 year in the CK and 3DCRT groups, respectively. In conclusion, in this cohort of patients with inoperable stage I peripheral NSCLC, CK appears to be a safe and superior alternative to conventionally fractionated radiotherapy.

Prognostic value of FDG uptake in primary inoperable non-small cell lung cancer.

The purpose of this study was to assess the prognostic value of 18F-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) in therapy for non-small cell lung cancer (NSCLC) and to further analyze the possible risk factors contributing to overall survival (OS) and progression-free survival (PFS). We retrospectively analyzed fifty patients between June 2007 and June 2010 with NSCLC who underwent positron emission tomography/computed tomography. We examined the correlation of the maximum standardized uptake value (SUVmax) in FDG-PET of the primary tumor with other possible factors. The FDG uptake in the primary tumor was also compared for the different Union for International Cancer Control (UICC) staging groups and further correlation was analyzed. We divided the patients into two groups by the receiver operating characteristic curve of SUVmax: SUVmax < 5.45 (low-SUV) and ≥ 5.45 (high-SUV). The prognostic value of each parameter for OS and PFS was determined by using univariate and multivariate analysis. There were significant correlations between SUVmax and Tumor length, N stage, UICC stage, histologic differentiation (r = 0.298, 0.855, 0.345, 0.435). The comparison between the low- and high-SUV groups was evaluated. Statistically significant differences were found in the SUVmax of the primary tumors among different UICC staging groups, and the correlation between stages I-II and stages III-IV for OS and PFS was also statistically significant. Univariate analysis showed that performance status (PS-ZPS score), histologic differentiation, UICC stages, and SUVmax of the primary tumor were significantly associated with OS and PFS. Multivariate logistic analysis showed that histologic differentiation and SUVmax of primary tumor might be considered as significant predictive factors for OS and PFS in patients with NSCLC. Our results showed that there was a significant relationship between the SUVmax of the primary tumor and OS and PFS. FDG uptake by the primary tumor may be an independent outcome predictor for patients with NSCLC.

A study on the effect of aqueous extract of Lobelia chinensis on colon precancerous lesions in rats.

This paper studies the effects of Lobelia chinensis on colon precancerous lesions and on colonic epithelial proliferation and apoptosis in DMH-induced rats. After two weeks of feeding, 50 Wistar rats were randomly divided into five groups, namely the normal group, model group, Lobelia chinensis low-dose group, medium-dose group and high-dose group. Lobelia chinensis was made into ACF model, and administered to experimental groups for 10 consecutive weeks. Control group was given equivalent amount of normal saline. After feeding for 10 weeks, the rats in each group were sacrificed and the changes in colonic ACF number of rats in experimental groups were observed, and the inhibition rates were calculated. The results showed that among the rats fed for 24 h and 48 h, the number of apoptotic cells in colonic crypts of rats in DMH group did not differ significantly from the control group, while the difference was obvious between the control group and Lobelia chinensis treatment groups. The medium and high doses, that is, 0.45 g/kg and 1.35 g/kg can significantly inhibit ACF formation (P<0.01). The inhibition rates of low, medium and high doses were 8.12%, 59.42% and 65.44%, respectively.